The overall goal of the renewal of this program project is to delineate the pathologic features of a chronic obstructive lung disease (COLD) resembling emphysema induced in the rat by exposure to NO2 and O3, separately and simultaneously. The epidemiologic importance of tobacco smoke in OLD has been established, and a principal objective will be to examine the demonstrated toxicity of cadmium salts, a component of tobacco smoke together with oxides of nitrogen. Cadmium will be examined as was O3, as a single compound and as a mixture with NO2. Short- and long-range experiments with both subacute and realistically low dosage schedules are planned for rats, as in our extensive previous research. Cigarette-level concentrations of cadmium salts alone will be examined first. Then the pathological, physiological, biochemical, histochemical, and hematological effects of cadmium alone and mixed with NO2 will be studied. Assessment of the vulnerability of animals to injury by photochemical oxidants at various stages of life will be continued to include prenatal and neonatal rats and pregnant and nursing mothers; aged rat cytology will also be studied by autoradiography. The five projects generally will use animals in common, supplied from the core exposure facility, and observations by the various techniques will be correlated by the participants. Emphasis will be on specific mechanisms involved in the long-range development of irreversible COLD. Attention will be given also to the stage of reversibility as well as to its entrenchment as a progressive and irreversible process.